Despite major efforts aimed at finding a treatment for Alzheimer's disease, progress in developing compounds that can relieve cognitive deficits associated with the disease has been slow. ANAVEX2-73 or A-273 (tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride) is a compound which is believed to bind to sigma-1 and muscarinic acetylcholine receptors with affinities in the low micromolar range. ANAVEX2-73 has the chemical structure:

The sigma-1 receptor is a chaperone protein in the endoplasmic reticulum (ER) that chaperones the IP3 receptor at the ER and mitochondrion interface to ensure proper Ca2+ signaling from the ER into the mitochondrion. Under pathological conditions in which cells encounter stress that results in the ER losing its global Ca2+ homeostasis, the sigma-1 receptor translocates and counteracts the arising apoptosis. As a result, the sigma-1 receptor is a receptor chaperone essential for the metabotropic receptor signaling and for the survival against cellular stress. See Centr. Nerv. Syst. Agents Med. Chem. 9(3), 184-189 (2009).
It has been reported that ANAVEX2-73 showed neuroprotective potential against amyloid toxicity in mice. In particular, ANAVEX2-73 has been reported as attenuating oxidative stress, caspases induction, cellular loss and learning and memory deficits observed in mice one week after the i.c.v. injection of an oligomeric preparation of amyloid β25-35 peptide (Aβ25-35). See J. Psychopharmacol. 25(8), 1101-1117 (2011). More recently, it has been reported that ANAVEX2-73 blocked the Aβ25-35-induced P-Akt decrease and P-GSK-3β increase, indicating activation at the PI3K neuroprotective pathway. See Neuropsychopharmacology 38, 1706-1723 (2013). In the dose-range tested, ANAVEX2-73 attenuated the hyperphosphorylation of Tau on physiological epitopes (AT-8 antibody clone) and on pathological epitopes (AT-100 clone). ANAVEX2-73 also has been reported to decrease the Aβ25-35-induced endogenous Aβ1-42 seeding.
Reference is made to U.S. Patent Publication No. 2014/0296211 entitled “ANAVEX2-73 AND CERTAIN ANTICHOLINESTERASE INHIBITORS COMPOSITION AND METHOD FOR NEUROPROTECTION,” to Vamvakides et al., filed Jul. 12, 2013; U.S. Ser. No. 62/065,833 entitled “A19-144, A2-73 AND CERTAIN ANTICHOLINESTERASE INHIBITOR COMPOSITIONS AND METHOD FOR ANTI-SEIZURE THERAPY,” filed Oct. 20, 2014; U.S. Patent application entitled “CRYSTAL FORMS OF TETRAHYDRO-N,N-DIMETHYL-2,2-DIPHENYL-3-FURANMETHANAMINE HYDROCHLORIDE, PROCESSES OF MAKING SUCH FORMS, AND THEIR PHARMACEUTICAL COMPOSITIONS” and filed on date even herewith; U.S. Patent application entitled “ENANTIOMERS OF A2-73, ANALOGUES, AND SIGMA AGONIST ACTIVITY” and filed on date even herewith. The teaching of these applications and publications and all references cited herein are incorporated by reference in their entirety.